Subjects were participants in the Baltimore Longitudinal Study of Aging. Plasma samples were obtained during an oral glucose tolerance test and insulin was measured by radioimmunoassay. Cross-sectional and longitudinal analyses were employed to gain insight into the complex inter-relationships among post-load and fasting plasma insulin levels and age, sex, obesity, fat distribution, lipids, and blood pressure. Due to the increased morbidity associated with hyperlipidemia, hypertension, hyperinsulinemia and obesity, the projects were directed toward attempting to determine the causal order, if one exists, among these metabolic variables as well as the roles of sex and aging. From the cross-sectional findings of this project it can be concluded that: (l) Correlations of blood pressure with plasma insulin levels after adjustments for age, obesity, and fat distribution were entirely non-significant. 2) Sex differences in fasting and post-load insulin levels are explained by differences in body habitus but insulin levels decline with age per se. In order to evaluate the potential role of insulin insensitivity as a cause of the glucose (G) intolerance of aging, we performed 230 hyperglycemic clamps, 85 on young (Y, 24 to 39 years), 47 on middle age (M, 40 to 59 years), and 98 on old (0, 60 to 90 years) carefully screened subjects of the Baltimore Longitudinal Study of Aging. The two hour plasma G levels on an oral glucose tolerance test were less than 140 mg/dl in Y and M and 180 mg/dl in 0. The old group was further dichotomized at 140 mg/dl into a "normal" group (ON) and an "impaired" group (OI). Four hyperglycemic plateau. were created: 3.0, 5.4, 7.9 and 12.8 mmol/L above basal. Three measures of glucose tolerance were derived: (1) G at 2 hours after glucose ingestion, (2) glucose utilization, M, at each hyperglycemic plateau, and (3) glucose decay constant, K, obtained at the conclusion of each clamp. These showed that the young group had the best glucose tolerance (Y'M-ON'OI). Despite these age differences in glucose tolerance, both the early and late phase plasma insulin responses during the clamp were remarkably similar among the groups. In contrast, insulin- dependent glucose uptake, a measure of tissue sensitivity to insulin, was decreased in the old-impaired group at every plateau. We conclude that healthy, active older subjects showed moderate intolerance to oral and IV glucose and that the major mechanism of this physiological aging process is decreased insulin sensitivity.